Evolution on experimental animal model for upper urothelium carcinogenesis.

Abstract

PURPOSE:

No optimal, well designed and reproducible animal model for upper urothelial carcinogenesis exists. This study characterized the histopathological features on top of immunolocalization of alpha-dystroglycans (alpha-DG) and matrix metalloproteinase (MMP-9) and cell turn-over in the upper urinary tract using a novel experimental model.

METHODS:

Seventy-five female Fischer 344 rats were divided into three groups: the control group received a 0.30-ml dose of 0.9% physiological saline; the MNU group (chemical carcinogen N-methyl-N-nitrosourea) received 0.30 ml of MNU; and the MNU-citrate group received 0.30 ml of MNU plus sodium citrate, every one intravesically every other week for a total of 4 doses. After 15 weeks, bladder, ureters and renal pelvis were collected for morphological and molecular analysis.

RESULTS:

Associated management with MNU and sodium citrate was able to lead to 100% of both urinary bladder and upper urinary tract tumors, being the high-grade noninvasive papillary urothelial carcinoma the most frequent lesion. The upper urothelium showed reduced alpha-DG and increased MMP-9 and Ki-67 immunoreactivities in the MNU-citrate group in relation to the other groups. MNU group presented no upper urothelium tumor and 100% bladder tumor.

CONCLUSIONS:

This is a relevant evolution on experimental animal model for upper urinary tract carcinogenesis field. MMP-dependent disruption of the DG complex plays an important role in urothelial tumor carcinogenesis and showed the model applicability and significance. MNU-citrate model could contribute to a better understanding of human upper urothelial cancer development as well as to its local treatment strategies in a near future.

• Authors: Leonardo O Reis, Wagner J Fávaro, Ubirajara Ferreira, Athanase Billis, Mariana G Fazuoli, Valéria H A Cagnon
• Journal: World journal of urology (World J Urol) Vol. 28 Issue 4 Pg. 499-505 (Aug 2010) ISSN: 1433-8726 [Electronic] Germany
• PMID: 20373103 (Publication Type: Journal Article)

Chemical References

• Alkylating Agents
• Citrates
• Sodium Citrate
• Methylnitrosourea

Topics

• Alkylating Agents (toxicity)
• Animals
• Biopsy
• Citrates (toxicity)
• Disease Models, Animal
• Female
• Kidney Medulla (diagnostic imaging, pathology)
• Methylnitrosourea (toxicity)
• Rats
• Rats, Inbred F344
• Sodium Citrate
• Ureter (diagnostic imaging, pathology)
• Urinary Bladder (diagnostic imaging, pathology)
• Urography
• Urologic Neoplasms (chemically induced, diagnostic imaging, pathology)
• Urothelium (diagnostic imaging, pathology)